THE IMMUNOPATHOGENESIS OF POLYMICROBIAL SEPSIS

This report deals with the advances made in the areas of complement and its role in sepsis, both in mice and in humans. The study relates to work over the past 25 years (late 1990s to October 2022). During this period, there has been very rapid progress in understanding the activation pathways of complement and the activation products of complement, especially the anaphylatoxin C5a and its receptors, C5aR1 and C5aR2. Much has also been learned about these pathways of activation that trigger activation of the innate immune system and the array of strong proinflammatory cytokines that can cause cell and organ dysfunction, as well as complement products that cause immunosuppression. The work in septic humans and mice, along with patients who develop lung dysfunction caused by COVID-19, has taught us that there are many strategies for treatment of humans who are septic or develop COVID-19-related lung dysfunction. To date, treatments in humans with these disorders suggest that we are in the midst of a new and exciting area related to the complement system.